This invention relates to mass spectroscopy and more particularly to ion cyclotron resonance spectroscopy.
This invention is an improvement of the method and apparatus for pulsed ion cyclotron resonance disclosed in U.S. Pat. No. 3,742,212, issued June 26, 1973, to Robert T. McIver, Jr., and is incorporated herein by reference. In U.S. Pat. No. 3,742,212, a method and apparatus is described for producing longer trapping periods to improve ion cyclotron resonance spectroscopy. The present invention provides an even greater increase in trapping time allowing storage of ions which permits analysis of samples at ultra-low pressures.
One of the major problems presently confronting mass spectrometry is analysis for low volatility compounds (i.e. compounds requiring ultra-low pressures for vaporization). This problem is especially acute in applications of mass spectrometry to studies of biological importance. In general, biological compounds exhibit high molecular weight, high polarity and the ability to form strong hydrogen bonds. Such compounds have low vapor pressures and sublime (i.e. vaporize) slowly even at elevated temperatures. The traditional approach to this problem has been to chemically derivatize samples in order to enhance volatility. However, chemical modification not only increases the molecular weight, but also is time consuming, difficult, and uncertain, especially when only small samples are available for analysis.
A number of new methods have been introduced recently for the analysis for low volatility compounds. Field desorption mass spectrometry has proved useful for a large number of polar compounds of low volatility. Rapid heating of a sample dispersed on a Teflon surface has been shown to greatly increase the rate of sample evaporation relative to competing surface decomposition reactions. Underivatized oligopeptides have been analyzed in a high pressure chemical ionization source by inserting a solid-sample probe directly in the plasma of reagent ions.
The analytical potential of the ion cyclotron resonance technique has been discussed and considered previously as in the patent referred to above. But despite some initial success in developing specific reagent ions, the scope of investigations has been severely restricted by the limited mass range and the low-mass resolution of the early instruments. Mass ranges have typically been limited to something below 200 to 250 atomic mass units (amu) and severely limited mass resolution beyond unit masses in the 200 amu because the residence time in the cell is relatively short. In addition, negative reagent ion studies under the relatively high pressure ionization conditions of present devices has thus far been almost non-existent.
Most ion cyclotron resonance mass spectrometers presently in existence are magnetic field sweep instruments. This mode of operation requires a high quality electromagnet and associated field sweep controls. Ions of a particular mass-to-charge ratio are detected by a marginal oscillator similar to those used to detect nuclear magnetic resonance. The plates of the analyzer cell are incorporated as capacitive elements in the resonant circuit of the marginal oscillator. When the resonant frequency of the marginal oscillator is equal to the cyclotron frequency of an ion, power is drawn from the resonant circuit as the ion is accelerated. A marginal oscillator is a very sensitive detector, but in spite of its wide use in detecting cyclotron resonance, a number of disadvantages and limitations are apparent. The resonant frequency of a marginal oscillator cannot be scanned conveniently over a wide frequency range. Instruments using a marginal oscillator detector must scan the magnetic field strength in order to trace out a mass spectrum. Electromagnets can be scanned over a wide range, but the rate of scanning is rather slow and the equipment needed for such scans is quite expensive. Another problem is that the mass range is severely limited by the intrinsic sensitivity of a marginal oscillator which is inversely proportional to the mass of the ion detected, and the fact that practical circuits do not perform well below about 75 kHz because of limitations in coil design.